Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Infection and Immunity Institute, Amsterdam, the Netherlands.
Cell Rep. 2020 Mar 24;30(12):4110-4123.e4. doi: 10.1016/j.celrep.2020.03.007.
Within lymph nodes (LNs), T follicular helper (T) cells help B cells to produce antibodies, which can either be protective or autoreactive. Here, we demonstrate that murine LN stromal cells (LNSCs) suppress the formation of autoreactive T cells in an antigen-specific manner, thereby significantly reducing germinal center B cell responses directed against the same self-antigen. Mechanistically, LNSCs express and present self-antigens in major histocompatibility complex (MHC) class II, leading to the conversion of naive CD4 T cells into T regulatory (T) cells in an interleukin-2 (IL-2)-dependent manner. Upon blockade of T cells, using neutralizing IL-2 antibodies, autoreactive T cells are allowed to develop. We conclude that the continuous presentation of self-antigens by LNSCs is critical to generate antigen-specific T cells, thereby repressing the formation of T cells and germinal center B cell responses. Our findings uncover the ability of LNSCs to suppress the early activation of autoreactive immune cells and maintain peripheral tolerance.
在淋巴结 (LNs) 中，滤泡辅助 T 细胞 (Tfh) 帮助 B 细胞产生抗体，这些抗体可以是保护性的，也可以是自身反应性的。在这里，我们证明了小鼠 LN 基质细胞 (LNSCs) 以抗原特异性的方式抑制自身反应性 T 细胞的形成，从而显著减少针对同一自身抗原的生发中心 B 细胞反应。从机制上讲，LNSCs 在主要组织相容性复合体 (MHC) 类 II 中表达和呈递自身抗原，导致幼稚 CD4 T 细胞在白细胞介素 2 (IL-2) 依赖性方式下转化为调节性 T (Treg) 细胞。在用中和 IL-2 抗体阻断 T 细胞后，允许自身反应性 T 细胞发育。我们得出结论，LNSCs 持续呈递自身抗原对于产生抗原特异性 T 细胞至关重要，从而抑制 T 细胞和生发中心 B 细胞反应的形成。我们的发现揭示了 LNSCs 抑制自身反应性免疫细胞早期激活和维持外周耐受的能力。
